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Nonetheless, despite effective virological control, PLWH are faced with accelerated aging, characterized by higher prevalence of age-related comorbidities than the general population. Persistent inflammation and activation of innate immunity seem to drive this immunosenescent phenotype. The cyclic GMP\u2013AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is increasingly recognized as a key player in the aging process and in age-related diseases, like cardiovascular and metabolic disorders, cancer, neurological diseases and cognitive decline. The human gene encoding for STING (STING1\/TMEM173) exhibit significant heterogeneity, with some common single nucleotide polymorphisms (SNPs) variably affecting its immune functions (R232H and R71H, G230A, R293Q, frequently co-segregating as HAQ haplotype). This study aims to investigate the impact of those hypomorphic variants on immune control, comorbidities, and cognitive and functional outcomes in a cohort of 60 aged (&gt;\u200950\u00a0years) chronic PLWH on stable ART. Patients were genotyped and differences in comorbidities, HIV-related clinical parameters, and cognitive and motor performances were assessed across genotype groups. Here we show that carriers of R71H, G230A and R293Q alleles were associated with a lower prevalence of dyslipidemia, while carriers of the R232H polymorphism show higher CD4\u207a T cell counts. Our results suggest that the common STING1\/TMEM173 polymorphisms may influence immunological and clinical outcomes, modulating lipid metabolism and the dynamics of immune recovery in these people.<\/jats:p>","DOI":"10.1007\/s11357-026-02561-9","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:42:24Z","timestamp":1790574144000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypomorphic STING1\/TMEM173 variants may support immuno-metabolic resilience in aging people living with HIV"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3902-3376","authenticated-orcid":false,"given":"Isabella","family":"Zanella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Fornari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4327-7305","authenticated-orcid":false,"given":"Federico","family":"Cesanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-871X","authenticated-orcid":false,"given":"Giorgio","family":"Tiecco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Zacchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bouros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2939-8553","authenticated-orcid":false,"given":"Silvia","family":"Codenotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-4583","authenticated-orcid":false,"given":"Rosalba Monica","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7475-2668","authenticated-orcid":false,"given":"Alessandro","family":"Fanzani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8137-4642","authenticated-orcid":false,"given":"Silvia","family":"Giliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1452-9100","authenticated-orcid":false,"given":"Eugenia","family":"Quiros-Roldan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"2561_CR1","unstructured":"UNAIDS, Global HIV & AIDS statistics \u2014 fact shee, available online https:\/\/www.unaids.org\/en\/resources\/fact-sheet (last accessed 26th February 2026)."},{"key":"2561_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-025-02045-1","author":"CG Wallace","year":"2026","unstructured":"Wallace CG, Capriotti Z, Klase Z. 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